Two aspects of cellular cooperation involving lymphocyte mediators and thought to be important in the pathogenesis of some rheumatic diseases will be examined. The first is lymphocyte mitogenic factor (LMF), a substance which mediates cooperation between lymphocyte subpopulations in man. Using a new and highly sensitive assay for this lymphokine based on stimulation of B lymphocyte proliferations, we propose to characterize and isolate LMF and fully define its mechanism of action and its cell surface receptor. Since certain rheumatic diseases may involve faulty T-B lymphocyte cooperation, we will investigate patients with rheumatic diseases such as systemic lupus erythematosus for possible faulty production of, or responsiveness to, LMF. The second aspect concerns lymphocyte cooperation resulting in the enhanced synthesis of complement components by human monocytes. We have demonstrated in preliminary experiments that antigen stimulated lymphocytes co-cultured with monocytes results in greatly enhanced C2 synthesis. A soluble mediator such as macrophage migration inhibitory factor (MIF) may be the means by which activated lymphocytes cause increased synthesis of C2 by monocytes. We propose to investigate this lymphocyte mediated regulation of complement synthesis by monocytes and examine its importance in disease states such as rheumatoid arthritis where increased local production of complement components has been demonstrated.